Giardia lamblia is the most common disease-causing parasite in the United States responsible for an estimated 3 million cases a year. Besides causing problems in day-care centers, travelers, backpackers, and homosexuals, the parasite not uncommonly contaminates water supplies and has been responsible for massive epidemics. The organism lives and multiplies in the small intestines and by unknown means causes diarrhea, abdominal pain, nausea and vomiting. Symptoms are frequently intermittent and long lasting. An environmentally resistant cyst form is passed in the feces, and, because large numbers of cysts are excreted and only a few can cause infection, giardiasis is a very common problem in the developed regions as well as undeveloped areas of the world. A major area of investigation is to understand how the parasite is able to survive in the body and how the body controls the infection. In animal models and likely in humans, some immunity to infection develops. Using mice made immune deficient in specific ways so that different parts of the immune system do not function, we were to show that cellular immunity and in particular "T" cells were critical in the control of the infection. Previously, antibodies were felt to be most important in curing infection so these findings were unexpected. Experiments are underway to understand how T cells are able to control Giardia infections. These studies will lead to a clearer understanding of how immunity develops, to characterization of the antigens important in provoking an immune response, and to eventually the development of a viable vaccine. One way organisms evade the immune response of the host is to change its surface. In this way, the parasite escapes the host's protective immune responses. Previously we showed that Giardia lamblia undergoes surface antigenic variation. The organism can use anywhere from 100 to150 different surface antigens. Using unique clones whose surface antigens can be detected using specific antibodies, we showed that clones behave differently in mice that are genetically unable to respond to the parasite. Therefore, organisms that only differ in their surface antigens are either preferred or eliminated in a host that lacks developmental immunity. Therefore, individual surface antigens are biologically unique. Furthermore, the same surface antigen type that is not preferred in mice is preferred in gerbils. The evidence indicates that the importance of the surface antigens may be in allowing Giardia to adapt to different hosts and allow it to infect a greater number of different mammals. We also showed that changes in the surface antigen of the parasite in the host are caused by antibody response to the surface and this is different from the immune responses that control the infection. Therefore, in the host two processes determine what surface antigens are found on the parasite in the intestine. First, the surface antigen must be compatible with the intestine of the host and later the antibody responses allow selective destruction of antigens already expressed and survive a growth of parasites that have new antigens. Giardia is considered one of the most primitive cells that have a nucleus so that the study of the cellular biology gives us clues as to the nature of primitive organisms and how higher life evolved. Using monoclonal antibodies that react with specific proteins, we defined the location and genes for a number of structural proteins. Most of these proteins are involved in essential biological processes such as the ability to form cysts and cell division. There are a number of unique characteristics of these proteins in contrast to higher types and the purpose of them is being studied by having the organism make defective proteins.